PROJECT SUMMARY The oxytocin (OT) system is perhaps the most viable neurobiological target for enhancing social cognition in psychiatric disorders with compromised social function, including autism spectrum disorder (ASD). In animals, OT enhances neural responsiveness to social cues, thereby facilitating social recognition, attachment and reward. In humans with ASD, intranasal OT enhances brain reward system responses to social stimuli, increases gaze to the eyes of others, and improves social reciprocity. The efficacy of intranasal OT as a therapy for social disorders is limited by poor penetrance into the brain. In order to inform future translational applications, our goal is to gain a better understanding of the precise mechanisms by which OT influence social information processing in the context of intrinsic or extrinsic reward. Social learning involves social information processing in the context of reward and is paramount to normative social skill development, and the role of OT in this process is a central theme of the Center. We will sustain a highly coordinated, interdisciplinary research program involving an outstanding team of investigators to test the hypothesis that OT facilitates social learning by enhancing the flow of information across neural networks involved in salience and reward. Project scientists will use cutting-edge techniques to manipulate OT signaling in specific circuits during social engagement to understand how OT influences socially relevant neural communication. Project 1 will examine the effect of pharmacologically-evoked endogenous OT release during a social encounter on a social salience brain network in monogamous prairie voles that have high or low densities of OT receptors. Project 2 will perform simultaneous electrophysiological recordings in three brain regions that process social information and reward during social bond formation in prairie voles. Optogenetic manipulations of the circuit will be used to test causal relationships between OT- dependent neural activity and social attachment. Project 3 will analyze the influence of optogenetic stimulation of OT release and targeted genetic mutations on neural communication in rats in the context of a social learning paradigm using extrinsic reinforcers. A potential interaction of OT and cholinergic systems will be examined. Project 4 will record neural activity in these same brain regions following local OT infusion in rhesus macaques while performing an extrinsic reward-based social discrimination visual task. A Bioanalytic Core will provide vital histological, genotyping and neural molecular phenotyping services for the research Projects. An Administrative Core will manage all Center related activities (seminar series, meetings, Pilot Project grants), provide statistical consultation and coordinate outreach and training activities of Center personnel by strengthening existing relationships and forging new ones with numerous organizations. As a result, the Center will create a vibrant collaborative research, training and outreach environment that will have a national impact on mental health research. The data collected by Center faculty will have important translational implications that will inform novel strategies for treating social deficits in psychiatric disorders.